Abstract: FR-PO337
Using an Innovative N-of-1 Trial Approach Testing Efficacy of Salt Supplementation in Gitelman Syndrome
Session Information
- Genetic Diseases: Models, Mechanisms, Treatments
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1102 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Verploegen, Maartje F.A., Radboudumc Afdeling Nierziekten, Nijmegen, Gelderland, Netherlands
- Wieërs, Michiel L.a.j., Erasmus MC Afdeling Inwendige Geneeskunde, Rotterdam, Zuid-Holland, Netherlands
- Giardina, Federica, Radboudumc Department for Health Evidence, Nijmegen, Netherlands
- Trepiccione, Francesco, Universita degli Studi della Campania Luigi Vanvitelli Dipartimento di Scienze Mediche Traslazionali, Napoli, Campania, Italy
- Walsh, Stephen B., University College London Department of Renal Medicine, London, London, United Kingdom
- Hoorn, Ewout J., Erasmus MC Afdeling Inwendige Geneeskunde, Rotterdam, Zuid-Holland, Netherlands
- Nijenhuis, Tom, Radboudumc Afdeling Nierziekten, Nijmegen, Gelderland, Netherlands
Background
Gitelman syndrome is a rare hereditary salt-losing tubulopathy resulting in hypokalemic alkalosis and hypomagnesemia. Treatment practices to correct hypokalemia include high-dose potassium supplementation and potassium-sparing diuretics. Furthermore, ad libitum dietary salt intake is advised. The efficacy of supraphysiological salt supplementation has yet to be investigated. We aim to investigate this salt supplementation in an individualized manner using N-of-1 trials, which are crossover trials conducted in a single patient. This unique study design facilitates research into individual treatment effects.
Methods
We are currently performing multiple randomized, double-blind, placebo-controlled N-of-1 trials in patients with symptomatic, genetically-proven Gitelman syndrome. Sodium chloride (NaCl; 12 gr/day) and placebo are compared during 6 consecutive four-week treatment periods (3 periods of each treatment). Treatment periods are randomly allocated. After each treatment period, outcome parameters, among which serum potassium and symptoms, are measured. Because of the N-of-1 design, the data of each patient will be analyzed individually to draw conclusions about the effect of salt supplementation in that individual patient. Finally, all N-of-1 trials will be aggregated to draw conclusions at group level.
Results
Currently, five patients have completed their N-of-1 trial. Preliminary analyses demonstrate that NaCl supplementation increased serum potassium in three patients with a mean of 0.13 mmol/l, 0.17 mmol/l, and 0.35 mmol/l, respectively. In the other two patients, no increase in potassium was apparent. During Kidney Week in November 2022, we will be able to present the results of 12 patients that have completed an N-of-1 trial.
Conclusion
The N-of-1 trial is an inventive method producing an individualized verdict on the efficacy of an intervention and is suited for use in rare diseases. NaCl supplementation resulted in a clinically relevant increase in serum potassium in three out of five patients with Gitelman syndrome. The results of the ongoing N-of-1 trials will provide further insight into the effect of NaCl supplementation and might enable the (prior) identification of patients who benefit from NaCl supplementation.